Parkinson's disease (PD) is a devastating malady for which there is presently no cure. Moreover, there is also no means of arresting the progressive neurodegeneration experienced by most of those who suffer from it. Approximately 1.5 million Americans are afflicted by PD. Age appears to be a critical parameter in those that develop PD with those who are 50 and above being the largest group affected. Because this is a progressive disease with no known cure, interest remains high in refining treatment options involving cell transplantation as a possible therapy aimed at restoration and regeneration of the damaged dopaminergic circuitry in the brain. Crucial issues that must be confronted in the field of neural stem/progenitor cell transplantation (NPCs) include those pertaining to the delivery and survival of the cells in question. For cell replacement therapies to become a viable option for treatment of Parkinson's disease, several obstacles that derive from these issues must be overcome. For instance, it has been estimated that only 5-10% of cells transplanted into the central nervous system (CNS) survive post-transplantation, leaving only a small portion of the cells originally grafted to contribute in functional restoration. When considered at the most fundamental level, and as discussed further below, it is not even known with certainty that the cells that are delivered into the brain via the presently existing means and methods are alive either at the time of delivery or shortly thereafter, within the brain.
From a clinical perspective, the most pressing need in this field is one of improving cell survival following transplantation due to the low percentage of cells that survive in the host central nervous system. The vast majority of transplanted cells die within 24 hours of transplantation, and a significant fraction may be dead upon delivery, no matter their source or origin. Triggers that may initiate this neuronal death include: donor tissue hypoxia and hypoglycemia, mechanical trauma during the delivery process, free radicals, growth factor deprivation, and excessive extracellular concentrations of excitatory amino acids in the host brain tissues. Part of the underlying issue is that growth factor infusion has typically not been undertaken via the same catheter. More generally, the functional nature of the catheter, its placement in the brain, and the parameters of infusion all play critical roles in controlling the distribution of agents such as cell slurries. In addition, researchers have shown that increasing the amount of implanted tissue does not always increase the rates at which the cells survive and differentiate into dopamine-producing neurons in Parkinsonian models. Primate studies have shown that distributing small amounts of tissue over a larger area, i.e., in “micrografts” (as such procedures are called), results in significant areas of densely packed dopaminergic neurons. There is extensive outgrowth from these neurons as compared to subjects which were infused with a large amount of cell slurry in a very localized region (Sladek et al., 1998). These results and others have demonstrated that two important needs must be met: (1) it is imperative to deliver a highly-controlled amount of tissue (i.e., a fixed number of cells) into the host brain, and (2) a knowledge of cell viability at the delivery point is critical for moving in the direction of developing a clinically useful technique.
The prior art is largely silent on the issue of achieving satisfactory results for both of these needs simultaneously during the delivery process. For instance, Goldman et al. in U.S. Pat. No. 7,037,493 disclose a method and means for delivering a nucleic acid that codes for a neurotrophic factor, but their method and means does not allow the clinical user to perform in situ monitoring of the cells in order to make acute assessments of their viability upon delivery and chronic assessment of their functionality post-delivery. Similarly, Hammer et al. in U.S. Pat. No. 6,758,828 teach methods and means for cell storage and delivery but do not disclose techniques for monitoring cell number and viability during delivery. Gay et al. in their abstract “Development of a Combination Cell Delivery/Biosensor Catheter for the Monitoring of Dopamine from Differentiated Neuronal Cells,” The Virginia Journal of Science, Vol. 55, p. 28, (2004), suggest a multi-probe means for introducing sensing instrumentation into a target location within the brain of a patient via a neurocatheter means, but that system is not designed for the cytometric monitoring and assessment of the cells during the delivery process.
A limitation of the prior art is that in general it discloses no methods or means for confirming cell viability during the delivery process. A second limitation of the prior art is that in general it discloses no methods or means for cytometrically counting the number of cells that traverse the catheter and enter the brain during the delivery process. Another limitation of the prior art is that it does not foresee photo-optical means to carry out the functions of viability confirmation and NPC cytometry in situ during the cell delivery process. Still another limitation of the prior art is that it does not foresee the incorporation of photo-optical means into neurocatheterization devices for the purpose of carrying out the in situ viability confirmation and NPC cytometry during the cell delivery process.
To lay the foundation for overcoming these limitations, means and methods for the incorporation of optical fibers into neurocatheters for use during the delivery of cells and other therapeutic agents into the brain were invented. This invention teaches methods and means for coupling the optical fibers into specialized distal tips of neurocatheters such that the optical fibers have full functionality in techniques for viability confirmation and NPC cytometry during the cell delivery process.